A mechanosensory system governs myosin II accumulation in dividing cells

Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Molecular biology of the cell (Impact Factor: 4.47). 02/2012; 23(8):1510-23. DOI: 10.1091/mbc.E11-07-0601
Source: PubMed


The mitotic spindle is generally considered the initiator of furrow ingression. However, recent studies suggest that furrows can form without spindles, particularly during asymmetric cell division. In Dictyostelium, the mechanoenzyme myosin II and the actin cross-linker cortexillin I form a mechanosensor that responds to mechanical stress, which could account for spindle-independent contractile protein recruitment. Here we show that the regulatory and contractility network composed of myosin II, cortexillin I, IQGAP2, kinesin-6 (kif12), and inner centromeric protein (INCENP) is a mechanical stress-responsive system. Myosin II and cortexillin I form the core mechanosensor, and mechanotransduction is mediated by IQGAP2 to kif12 and INCENP. In addition, IQGAP2 is antagonized by IQGAP1 to modulate the mechanoresponsiveness of the system, suggesting a possible mechanism for discriminating between mechanical and biochemical inputs. Furthermore, IQGAP2 is important for maintaining spindle morphology and kif12 and myosin II cleavage furrow recruitment. Cortexillin II is not directly involved in myosin II mechanosensitive accumulation, but without cortexillin I, cortexillin II's role in membrane-cortex attachment is revealed. Finally, the mitotic spindle is dispensable for the system. Overall, this mechanosensory system is structured like a control system characterized by mechanochemical feedback loops that regulate myosin II localization at sites of mechanical stress and the cleavage furrow.

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Available from: Douglas N Robinson, Oct 04, 2015
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    • "However, the exact geometry of F-actin and Myosin II filaments in the contractile ring is still a matter of debate and alternative models for contractile ring organization and constriction have been proposed [Reichl et al., 2008; Carvalho et al., 2009; Kee et al., 2012; Ma et al., 2012; reviewed in Green et al., 2012]. Recent studies in Dictyostelium and vertebrate cells have led to the proposal that Myosin II does not translocate actin, but is required to cross-link actin filaments and to exert tension on actin during cytokinesis [Reichl et al., 2008; Kee et al., 2012; Ma et al., 2012]. As the ring constricts, the cross-sectional area of the ring is stable, suggesting the importance of a balance between Factin polymerization and disassembly during cytokinesis. "
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    ABSTRACT: Cytokinesis separates the genomic material and organelles of a dividing cell equitably into two physically distinct daughter cells at the end of cell division. This highly choreographed process involves coordinated reorganization and regulated action of the actin and microtubule cytoskeletal systems, an assortment of motor proteins, and membrane trafficking components. Due to their large size, the ease with which exquisite cytological analysis may be performed on them, and the availability of numerous mutants and other genetic tools, Drosophila spermatocytes have provided an excellent system for exploring the mechanistic basis for the temporally programmed and precise spatially localized events of cytokinesis. Mutants defective in male meiotic cytokinesis can be easily identified in forward genetic screens by the production of multinucleate spermatids. In addition, the weak spindle assembly checkpoint in spermatocytes, which causes only a small delay of anaphase onset in the presence of unattached chromosomes, allows investigation of whether gene products required for spindle assembly and chromosome segregation are also involved in cytokinesis. Perhaps due to the large size of spermatocytes and the requirement for two rapid-fire rounds of division without intervening S or growth phases during meiosis, male meiotic mutants have also revealed much about molecular mechanisms underlying new membrane addition during cytokinesis. Finally, cell type-specific differences in the events that set up and complete cytokinesis are emerging from comparison of spermatocytes with cells undergoing mitosis either elsewhere in the organism or in tissue culture. © 2012 Wiley Periodicals, Inc.
    Cytoskeleton 11/2012; 69(11). DOI:10.1002/cm.21063 · 3.12 Impact Factor
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    • "This principle explains the ability of cells lacking myosin II to perform cytokinesis [Neujahr et al., 1997; Zang and Spudich, 1998; Zhang and Robinson, 2005; Poirier et al., 2012], as well as the ability of certain mammalian cells to perform cytokinesis in the presence of blebbistatin, a myosin inhibitor [Straight et al., 2003; Kanada et al., 2005]. It also accounts for why myosin II mechanochemistry is not ratelimiting for furrow ingression and why in Dictyostelium, furrow ingression rates are inversely related to the length of the myosin II lever arm (if filament sliding were the primary mechanism for furrow constriction, the longer lever arm mutants would be expected to ingress faster) [Reichl et al., 2008; Kee et al., 2012]. This fundamental principle has also been implicated in mammalian cells, where a mutant myosin II that has mechanosensitivity but no actin-filament sliding ability is able to support cytokinesis in cultured cells as well as during embryonic development [Ma et al., 2012]. "
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    ABSTRACT: Cytokinesis shape change occurs through the interfacing of three modules, cell mechanics, myosin II-mediated contractile stress generation and sensing, and a control system of regulatory proteins, which together ensure flexibility and robustness. This integrated system then defines the stereotypical shape changes of successful cytokinesis, which occurs under a diversity of mechanical contexts and environmental conditions. © 2012 Wiley Periodicals, Inc.
    Cytoskeleton 10/2012; 69(10):700-9. DOI:10.1002/cm.21045 · 3.12 Impact Factor
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    • "Thus, IQGAP1 is required for normal expression and cortical localization of cortexillins I and II. This is in contrast to single cells in which cortexillin I localizes to the cortex in the absence of IQGAP1 (Faix et al., 2001; Kee et al., 2012) (see Discussion). Next, we examined IQGAP1 and myosin localization in ctxAÀ culminants. "
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    ABSTRACT: Apical actomyosin activity in animal epithelial cells influences tissue morphology and drives morphogenetic movements during development. The molecular mechanisms leading to myosin II accumulation at the apical membrane and its exclusion from other membranes are poorly understood. We show that in the nonmetazoan Dictyostelium discoideum, myosin II localizes apically in tip epithelial cells that surround the stalk, and constriction of this epithelial tube is required for proper morphogenesis. IQGAP1 and its binding partner cortexillin I function downstream of α- and β-catenin to exclude myosin II from the basolateral cortex and promote apical accumulation of myosin II. Deletion of IQGAP1 or cortexillin compromises epithelial morphogenesis without affecting cell polarity. These results reveal that apical localization of myosin II is a conserved morphogenetic mechanism from nonmetazoans to vertebrates and identify a hierarchy of proteins that regulate the polarity and organization of an epithelial tube in a simple model organism.
    Developmental Cell 08/2012; 23(3):533-46. DOI:10.1016/j.devcel.2012.06.008 · 9.71 Impact Factor
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